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Arrhythmogenic cardiomyopathy is a familial heart muscle disease characterized by structural, electrical, and pathological abnormalities. Recognition of left ventricular (LV) involvement in arrhythmogenic right ventricular cardiomyopathy (ARVC) has led to the newer term of arrhythmogenic cardiomyopathy (ACM). We report on a family with autosomal dominant desmoplakin (DSP) related ACM to illustrate the broad clinical spectrum of disease. The importance of evaluation of relatives with cardiac magnetic resonance imaging and consideration of genetic testing in the absence of Task Force diagnostic criteria is discussed. The practical and ethical issues of access to the Guthrie collection for deoxyribonucleic acid (DNA) testing are considered.

Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients.This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM.Patients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout.From baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: -40 ± 27 mm Hg, and -43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (-36 ± 27 mm Hg and -53 ± 44 mm Hg, P = 0.001 and 0.0001 vs placebo, respectively). There were modest reductions in EF (-6% ± 7.5% and -12% ± 5.9%, P = 0.007 and P0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro-B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms.Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM.

Peripartum cardiomyopathy (PPCM) is an important cause of maternal and infant mortality worldwide. Although heart failure presenting in the puerperium is well recognized, PPCM is a distinct cardiomyopathy that requires a high index of suspicion for diagnosis. There are known risk factors, but the aetiology and natural history of this disorder are not fully understood. The past decade has seen an increase in knowledge about the epidemiology, pathophysiology and genetics of this condition, leading to the first treatment trials, alongside international guidelines and registries.

In 2022, the British Cardiovascular Society celebrates the centenary of its foundation. Starting out as a small group of government-appointed physicians interested in heart disease, the Cardiac Club has grown and adapted to represent all those working in cardiovascular care and research. The historical stages of the organisation’s development are outlined, alongside major innovations in science and technology providing context for a rapidly changing medical world. Only a small part of the history of cardiology in Britain is told, with greater emphasis on describing the broader need for services, skilled workforce, healthcare policy and continuing education. Above all, the history of the British Cardiovascular Society is a story of people and places. The people are those with vision, attitude and leadership to improve the care of communities across the world. The places are those that enabled conversation, innovation and freedom to bring about change. It is hard to believe the remarkable progress in diagnosis, prevention and treatment of heart disease over 100 years, but a thriving modern Society must be the greatest legacy of its founders.

Background Myocardial fibrosis is a common feature of hypertrophic cardiomyopathy (HCM) but its pathophysiology has yet to be elucidated. Purpose In this study, we used a multiplex approach to examine the genetic regulation of pathways associated with fibrosis in patients undergoing septal myectomy. Methods Myocardial tissue was collected at time of surgical intervention. Control biopsy samples were obtained from the left ventricular free wall from structurally normal hearts during autopsy following non-cardiac related death. Tissue was either snap frozen in liquid nitrogen and subsequently stored at −80 degrees or collected in RNA laterTM and frozen 24 hours later at −80 degrees. Total RNA was extracted from HCM tissue samples using the Qiagen RNeasy fibrous tissues mini kit and from control samples using mirVana isolation kit (Ambion), according to the manufacturer's protocol. Quantitative PCR (qPCR) was performed on the extracted RNA using a RT. Profiler™ Human finrosis PCR Array. Results The study cohort comprised 22 HCM samples and 5 controls. The relative regulation of genes involved in myocardial fibrosis in patients with HCM compared to controls is shown in figure 1. In patients with HCM, there was increased expression of genes involved in collagen synthesis. A significant two-fold upregulation in type III procollagen mRNA was observed relative to controls (p=0.013) with a similar trend identified for type I procollagen (1.5 fold up-regulation, p=0.081). The gene expression of MMP3 (−1.5 fold, p=0.029) and MMP8 (−1.8, p=0.002) which are involved in collaged degradation were downregulated in the HCM group. The gene expression of pro-fibrotic mediators TGF-β2 (4.8 fold, p=0.008) and CCN2 (2.9 fold, p=0.021) was also significantly elevated. Within the HCM group, there was a correlation between the fold regulation of TGF-β1 (r=0.570, p=0.006; r=0.528, p=0.012), TGF-β2 (r=0.569, p=0.006; r=0.514, p=0.014) and TGF-β3 (r=0.738, p The expression of BMP-7 which has been shown to reduce myocardial fibrosis by antagonising TGF- β mediated endothelial – mesothelial transformation of fibroblasts was also down-regulated in HCM (−3.8, p=0.015). Conclusions Genetic expression of procollagen is significantly upregulated in patients with HCM relative to controls. TGF-β and CCN2 mediated signalling appear to be key mediators in promoting collagen expression. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Heart Hospital Charitable Grant, UK Figure 1. Gene expression in HCM

ObjectiveWe provide succinct, evidence-based and/or consensus-based best practice guidance for the cardiac care of children living with Duchenne muscular dystrophy (DMD) as well as recommendations for screening and management of female carriers of mutations in theDMD-gene.MethodsInitiated by an expert working group of UK-based cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK-cardiologists, consensus was reached on these best-practice recommendations for cardiac care in DMD.ResultsThe resulting recommendations are presented in the form of a succinct care pathway flow chart with brief justification. The guidance signposts evidence on which they are based and acknowledges where there have been differences in opinion. Guidelines for cardiac care of patients with more advanced cardiac dystrophinopathy at any age have also been considered, based on the previous published work of Quinlivanet aland are presented here in a similar format. The recommendations have been endorsed by the British Cardiovascular Society.ConclusionThese guidelines provide succinct, reasoned recommendations for all those managing paediatric patients with early or advanced stages of cardiomyopathy as well as females with cardiac dystrophinopathy. The hope is that this will result in more uniform delivery of high standards of care for children with cardiac dystrophinopathy, so improving heart health into adulthood through timely earlier interventions across the UK.

Holt-Oram syndrome (HOS) is a rare, autosomal dominant disorder caused by heterozygous pathogenic variants in cardiac T-box transcription factor, TBX5. Classically, it is associated with upper limb malformations and variable cardiac abnormalities. Limb manifestations are considered to be invariably present, ranging in severity from limitation in movement, to triphalangeal thumbs, absent thumbs, shortened forearms, or phocomelia. Cardiac involvement is characterized by congenital heart defects, most commonly septal structural malformations, and conduction system disease. Recently, novel TBX5 variants have also been reported in association with dilated cardiomyopathy (DCM). In this context, we report eight individuals from four unrelated families, in whom pathogenic variants in TBX5 segregated with an atypical HOS phenotype. Affected individuals exhibit relatively mild skeletal features of HOS, with a predominant cardiac phenotype, which includes several individuals affected by non-ischaemic DCM. To our knowledge, these represent the first reported cases of DCM in families with skeletal features of HOS, some of whom also harbored variants previously linked to a classical HOS phenotype (p. Arg279* and p.Arg237Gln). This finding supports diverse roles of TBX5 in cardiovascular development and function, and confirms the importance of long-term cardiac surveillance for individuals affected by HOS. Furthermore, these families highlight the wide phenotypic variability of HOS, which may include comparatively mild upper limb findings in respect to cardiac manifestations.

Hypertrophic cardiomyopathy (HCM) is defined by pathological left ventricular hypertrophy (LVH). It is the commonest inherited cardiac condition and a significant number of high risk cases still go undetected until a sudden cardiac death (SCD) event. Plasma biomarkers do not currently feature in the assessment of HCM disease progression, which is tracked by serial imaging, or in SCD risk stratification, which is based on imaging parameters and patient/family history. There is a need for new HCM plasma biomarkers to refine disease monitoring and improve patient risk stratification. To identify new plasma biomarkers for patients with HCM, we performed exploratory myocardial and plasma proteomics screens and subsequently developed a multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay to validate the 26 peptide biomarkers that were identified. The association of discovered biomarkers with clinical phenotypes was prospectively tested in plasma from 110 HCM patients with LVH (LVH+ HCM), 97 controls, and 16 HCM sarcomere gene mutation carriers before the development of LVH (subclinical HCM). Six peptides (aldolase fructose-bisphosphate A, complement C3, glutathione S-transferase omega 1, Ras suppressor protein 1, talin 1, and thrombospondin 1) were increased significantly in the plasma of LVH+ HCM compared with controls and correlated with imaging markers of phenotype severity: LV wall thickness, mass, and percentage myocardial scar on cardiovascular magnetic resonance imaging. Using supervised machine learning (ML), this six-biomarker panel differentiated between LVH+ HCM and controls, with an area under the curve of ≥ 0.87. Five of these peptides were also significantly increased in subclinical HCM compared with controls. In LVH+ HCM, the six-marker panel correlated with the presence of nonsustained ventricular tachycardia and the estimated five-year risk of sudden cardiac death. Using quantitative proteomic approaches, we have discovered six potentially useful circulating plasma biomarkers related to myocardial substrate changes in HCM, which correlate with the estimated sudden cardiac death risk.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by a complex phenotype that is only partly explained by the biological effects of individual genetic variants. The aim of this study was to use proteomic analysis of myocardial tissue to explore the postgenomic phenotype. Methods: Label-free proteomic analysis was used initially to compare protein profiles in myocardial samples from 11 patients with HCM undergoing surgical myectomy with control samples from 6 healthy unused donor hearts. Differentially expressed proteins of interest were validated in myocardial samples from 65 unrelated individuals (HCM [n=51], controls [n=7], and aortic stenosis [n=7]) by the development and use of targeted multiple reaction monitoring-based triple quadrupole mass spectrometry. Results: In this exploratory study, 1586 proteins were identified with 151 proteins differentially expressed in HCM samples compared with controls ( P P P P =0.015), late gadolinium enhancement on cardiac magnetic resonance imaging ( P =0.03) and the presence of a pathogenic sarcomere mutation ( P =0.04). Conclusions: The myocardial proteome of HCM provides supporting evidence for dysregulation of metabolic and structural proteins. The finding that lumican is raised in HCM hearts provides insight into the myocardial fibrosis that characterizes this disease.

Background— Exercise testing is performed in patients with hypertrophic cardiomyopathy to evaluate blood pressure response, a risk factor for sudden cardiac death. The prognostic role of exercise gas exchange variables is unknown. Methods and Results— Between 1998 and 2010, 1898 patients (age 47±15 years, range 16–86 years; 67% male) with hypertrophic cardiomyopathy underwent cardiopulmonary exercise testing. A total of 178 (9.4%) patients reached the primary end point of all-cause mortality or heart transplant (death/transplant) during a median follow-up of 5.6 years (interquartile range 2.6–8.9), giving an annual event rate of 1.6% per person year. Peak oxygen consumption (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.77–0.88, P P =0.049), and ventilatory anaerobic threshold (adjusted HR 0.82, 95% CI 0.70–0.96, P =0.016) were predictors of the primary outcome after correction for age, sex, left atrial size, nonsustained ventricular tachycardia, and ejection fraction. The overall adjusted death/transplant estimates for patients in the lowest quartile with peak oxygen consumption ≤15.3 mL/kg/min were 14% at 5 years and 31% at 10 years. Peak oxygen consumption (HR 0.81, 95% CI 0.77–0.86, P P Conclusions— Cardiopulmonary exercise testing provides prognostic information in patients with hypertrophic cardiomyopathy. Submaximal exercise parameters, such as ventilatory efficiency and anaerobic threshold, measured alone or in combination with peak oxygen consumption, predict death from heart failure.

Cardiomyopathies are an important cause of sudden cardiac death in young people and are responsible for arrhythmias and premature heart failure in all age groups. Although many cardiomyopathies are inherited, biochemical markers are a fundamental part of the diagnostic work-up and are useful in the prognostic assessment of disease. In this article, the authors review the rationale and evidence for important biomarkers according to their role in patient management. Emerging biomarkers are briefly reviewed, alongside modern scientific approaches to biomarker discovery.

Background Anderson–Fabry Disease (AFD) is an X linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Some mutations are associated with prominent and, in many cases, exclusive cardiac involvement. The primary aims of this study were to determine the incidence of major cardiac events in AFD and to identify clinical and genetic predictors of adverse outcomes. Methods and results We studied 207 patients with AFD (47% male, mean age 44 years, mean follow-up 7.1 years). Fifty-eight (28%) individuals carried mutations that have been previously associated with a cardiac predominant phenotype. Twenty-one (10%) developed severe heart failure (New York Heart Association functional class (NYHA) ≥3), 13 (6%) developed atrial fibrillation (AF), 13 (6%) received devices for the treatment of bradycardia; there were a total of 7 (3%) cardiac deaths. The incidence of the primary endpoint (a composite of new onset AF, NYHA ≥ 3 symptoms, device insertion for bradycardia and cardiac death) was 2.64 per 100 person-years (CI 1.78 to 3.77). Age (HR 1.04, CI 1.01 to 1.08, p=0.004), Mainz Severity Score Index score (HR 1.05, CI 1.01 to 1.09, p=0.012) and QRS duration (HR 1.03, CI 1.00 to 1.05, p=0.020) were significant independent predictors of the primary endpoint. The presence of a cardiac genetic variant did not predict the primary end point. Conclusions AFD is associated with a high burden of cardiac morbidity and mortality. Adverse cardiac outcomes are associated with age, global disease severity and advanced cardiac disease but not the presence of cardiac genetic variants.

Importance Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy. Objective To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid β-oxidation, on exercise capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. Design, Setting, and Participants This randomized, placebo-controlled, double-blind clinical trial at The Heart Hospital, University College London Hospitals, London, United Kingdom was performed between May 31, 2012, and September 8, 2014. The trial included 51 drug-refractory symptomatic (New York Heart Association class ≥2) patients aged 24 to 74 years with a maximum left ventricular outflow tract gradient 50 mm Hg or lower and a peak oxygen consumption during exercise of 80% or less predicted value for age and sex. Statistical analysis was performed from March 1, 2016 through July 4, 2018. Interventions Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months. Main Outcomes and Measures The primary end point was peak oxygen consumption during upright bicycle ergometry. Secondary end points were 6-minute walk distance, quality of life (Minnesota Living with Heart Failure questionnaire), frequency of ventricular ectopic beats, diastolic function, serum N-terminal pro–brain natriuretic peptide level, and troponin T level. Results Of 49 participants who received trimetazidine (n = 26) or placebo (n = 23) and completed the study, 34 (70%) were male; the mean (SD) age was 50 (13) years. Trimetazidine therapy did not improve exercise capacity, with patients in the trimetazidine group walking 38.4 m (95% CI, 5.13 to 71.70 m) less than patients in the placebo group at 3 months after adjustment for their baseline walking distance measurements. After adjustment for baseline values, peak oxygen consumption was 1.35 mL/kg per minute lower (95% CI, −2.58 to −0.11 mL/kg per minute;P = .03) in the intervention group after 3 months. Conclusions and Relevance In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited. Trial Registration ClinicalTrials.gov identifier:NCT01696370

Hypertrophic cardiomyopathy is a common inherited heart muscle disorder associated with sudden cardiac death, arrhythmias and heart failure. Genetic mutations can be identified in approximately 60% of patients; these are commonest in genes that encode proteins of the cardiac sarcomere. Similar to other Mendelian diseases these mutations are characterized by incomplete penetrance and variable clinical expression. Our knowledge of this genetic diversity is rapidly evolving as high-throughput DNA sequencing technology is now used to characterize an individual patient’s disease. In addition, the genomic basis of several multisystem diseases associated with a hypertrophic cardiomyopathy phenotype has been elucidated. Genetic biomarkers can be helpful in making an accurate diagnosis and in identifying relatives at risk of developing the condition. In the clinical setting, genetic testing and genetic screening should be used pragmatically with appropriate counseling. Here we review the current role of genetic biomarkers in hypertrophic cardiomyopathy, highlight recent progress in the field and discuss future challenges.

Hypertrophic cardiomyopathy is a heterogeneous clinical syndrome with a wide spectrum of pathophysiologic consequences. Most cases are inherited and caused by sarcomeric protein gene mutations, although phenocopies are often encountered. Genomic research and family studies have improved our recognition of the disease and understanding of its natural history; however, tenuous links exist between genotype and phenotype and thus far have done little to alter clinical management. Surgery and, more recently, implantable cardiac defibrillators have had an impact on sudden cardiac death rates, with improved short- and medium-term survival. Therefore, managing heart failure has become increasingly challenging. Although heart failure due to fibrosis and a progressive loss of contractile function is common, treatment remains largely empiric. Case series and animal studies suggest that biventricular pacing and renin-angiotensin-aldosterone system modifiers may be useful in some patients, but there is a need for large prospective randomized controlled trials to study these and other treatments. Risk stratification and eligibility for sports participation remain hot topics, but one of the greatest challenges is the management of a growing cohort of asymptomatic gene carriers identified during family screening. Ultimately, major advances in treatment and disease prevention will come from a better understanding of the genomic, proteomic, and metabolomic profiles of individual patients.

The modern description of hypertrophic cardiomyopathy is credited to the London pathologist, Robert Donald Teare who likened the disease to "a tumour of the heart" and published his observations in the British Heart Journal 50 years ago. Teare recognised asymmetrical hypertrophy and myocyte disarray as a familial condition associated with premature and sudden death in young people. He rightly deserves the accolade for bringing a poorly understood, but well recognised phenomenon into the public domain. Thick and heavy hearts had been of interest and investigation to physicians and pathologists for many centuries. This article reviews the early history of hypertrophic cardiomyopathy and reflects on several centuries of progress in our understanding of the condition.

Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening. Elucidation of the genetic basis of HCM lead to the identification of several genes encoding sarcomeric proteins, such as MYH7, MYBPC3, TPM1, TNNT2, and TNNI3. Sarcomeric genes are mutated in approximately 40% of HCM patients and a possible explanation for the incomplete yield of mutation-positive HCM may be somatic mutations.We studied 104 unrelated patients with non-familial HCM. Patients underwent clinical evaluation and mutation screening of 5 genes implicated in HCM (MYH7, MYBPC3, TPM1, TNNT2, and TNNI3) in genomic DNA isolated from resected cardiac tissue; 41 of 104 were found to carry a mutation, but as several patients carried the same mutations, the total amount of different mutations was 37; 20 of these mutations have been previously described, and pathogenicity has been assessed. To determine the effect of the 17 new mutations an in silico assay was performed and it predicted that 4 variants were damaging mutations. All identified variants were also seen in the DNA isolated from the corresponding blood, which demonstrated the absence of somatic mutations.Somatic mutations in MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 do not represent an important etiologic pathway in HCM.

Aims To determine the relation between serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and prognosis in patients with hypertrophic cardiomyopathy (HCM). Methods and results In total, 847 patients (53 ± 15 years; 67% male) with HCM (28% with left ventricular outflow tract obstruction ≥30 mmHg at rest) were followed for 3.5 years (IQR 2.5–4.5 years). The median NT-proBNP concentration was 78 pmol/L (range

The European Society of Cardiology recently recommended a new tool 1 to estimate 5 year risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We investigated the relationship between serum cardiac troponin I (cTnI) levels and HCM-risk score in 100 consecutive patients referred to the West of Scotland Inherited Cardiac Conditions Clinic. The 20 most recent patients had a high sensitivity cTnI assay performed (limit of detection (LOD) 1.2 ng/L) and the remaining 80 had the traditional assay (LOD 10 ng/L). Demographic, clinical, genetic and imaging parameters were collected at first assessment. HCM-risk was calculated retrospectively. Cardiac TnI was elevated in 27% of the population (n = 100, 60% male, mean age 56 ± 14, left ventricular outflow tract (LVOT) obstruction (i.e. resting gradient ≥30 mmHg) in 20%) and they had significantly higher overall HCM-risk score (3.7% v 2.2%, p In conclusion, serum cTnI is elevated in a significant proportion of patients with HCM and is associated with clinical markers of disease severity. Biomarkers may be useful as an adjunct to current risk models in identifying patients with adverse cardiac remodelling and underlying atrial fibrillation. Reference O’Mahony C et al . A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur Heart J . 2014;35(30):2010-–20

Enzyme replacement therapy has the potential to delay or reverse adverse cardiac remodeling in Anderson-Fabry disease (AFD); however, the current indications for enzyme replacement therapy rely on detecting relatively advanced features of the disease. We aimed to determine the relation between the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and cardiac abnormalities in patients with AFD. We hypothesized that it might help to detect early disease. NT-proBNP was measured under at rest conditions in 117 patients with AFD (age 48 ± 15 years, 46.2% men). All patients underwent clinical evaluation with electrocardiography and echocardiography. The median NT-proBNP concentration was 24 pmol/L (range

Introduction The genetic background of hypertrophic cardiomyopathy (HCM) is well described; however it fails to explain the phenotypic diversity characteristic of the disease. By performing an unbiased label-free quantitative proteomics analysis of heart tissue, we have identified important proteins and pathways that contribute to the cytoskeletal and metabolic alterations of HCM. To verify and validate these findings we have developed a targeted and rapid peptide-based tandem mass spectrometry (MS/MS) assay to prospectively screen a large genotyped cohort of patients. Methods Heart tissue from 17 patients with HCM and 6 controls was homogenised and whole protein assayed, prior to tryptic digestion. Samples were analysed using PLGS Version 2.5 and quantified based on ion abundance using Progenesis LC-MS. Statistically significant differences were calculated by one-way ANOVA. Proteins were submitted for ontology and functional annotation bioinformatics. Selected differentially expressed proteins were validated in 59 patients by developing a targeted, high throughput, peptide-based multiple reaction monitoring (MRM) assay using a Waters Xevo TQ-S triple quadruple mass spectrometer. Further validation and localisation of proteins was confirmed with immunohistochemistry. Results 1672 unique proteins were identified of which 152 were differentially expressed between the 2 groups (p Conclusions This is the first comprehensive global proteomic study of human hypertrophic cardiomyopathy. We have identified differences in the expression of several proteins in the HCM heart, many of which are relevant to the disease process. By developing a targeted and multiplexed MS/MS based assay we have been able to prospectively validate potential biomarkers in tissue, and create an assay that can be applied to screen plasma. Increased myocardial expression of Lumican is a possible marker of progressive disease in HCM.

A 46-year-old woman was admitted following three episodes of collapse. She had no past medical history but her cousin had died suddenly in her 30s from an unknown heart condition. Physical examination and blood pressure were normal. An electrocardiogram (ECG) showed diffuse T wave inversion (figure 1), and troponin I measured at 12 h was 0.96 μg/l. Routine blood tests, inflammatory markers, coronary angiography and 24 h Holter …

A 53-year-old white man was identified through family screening as having arrhythmogenic right ventricular cardiomyopathy caused by a frameshift mutation in the desmoplakin gene (DSP S1015fsX1017). Direct questioning revealed a previously undisclosed history of palpitations. The electrocardiogram (ECG) showed anterolateral T-wave inversion (Figure 1). Holter monitoring detected an asymptomatic 11-beat run of nonsustained ventricular tachycardia, 2 triplets, 11 couplets, and 1754 multifocal ventricular ectopics. These ectopics were of left ventricular (LV) origin when captured on 12-lead ECG. There were no late potentials on signal-averaged ECG. Figure 1. ECG …